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The Journal of Neuroscience, May 1, 2000, 20(9):3254-3262
c-Raf Regulates Cell Survival and Retinal Ganglion Cell
Morphogenesis during Neurogenesis
Belén
Pimentel1,
Carmen
Sanz2,
Isabel
Varela-Nieto2,
Ulf R.
Rapp3,
Flora
De
Pablo1, and
Enrique J.
de la
Rosa1
1 Department of Cell and Developmental Biology, Centro
de Investigaciones Biológicas, Consejo Superior de
Investigaciones Científicas (CSIC), E-28006 Madrid, Spain,
2 Instituto de Investigaciones Biomédicas Alberto
Sols, CSIC-Universidad Autónoma de Madrid, E-28029 Madrid,
Spain, and 3 Institut für medizinische Strahlenkunde
und Zellforschung, University of Würzburg, D-97078 Germany
The signaling cascade Ras/Raf/mitogen-activated protein
kinases modulates cell proliferation, differentiation, and survival, all key cellular processes during neural development. To better define
the in vivo role of Raf during chick retinal
neurogenesis, we interfered with Raf-dependent signaling during days
4.5 to 7.5 of embryonic development by expressing a dominant negative mutant of c-Raf ( Raf), which blocks Ras-dependent Raf activation, and by overexpressing wild-type c-Raf. Raf expression induced an
increase in cell death by apoptosis, whereas it did not affect overall
cell proliferation and differentiation. In parallel, the number of
Islet-1/2-positive and TUJ1-positive retinal ganglion cells were
diminished in their definitive layer, whereas there was an increase in
the number of mislocated Islet-1/2-positive cells. This disturbed
morphogenesis correlated with a disruption of the optic fiber layer.
Conversely, c-Raf overexpression caused moderate opposite effects on
apoptosis. These results frame in vivo early
neurogenesis processes in which c-Raf is essential.
Key words:
apoptosis; cell death; cell survival; neural development; neurogenesis; retinal ganglion cell; signaling; chick embryo
Copyright © 2000 Society for Neuroscience 0270-6474/00/2093254-09$05.00/0
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